The insulin receptor with phenylalanine replacing tyrosine-1146 provides evidence for separate signals regulating cellular metabolism and growth

Journal Article · Tue May 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.9.3358· OSTI ID:5393994

Wilden, P A; Backer, J M; Kahn, C R; Cahill, D A; Schroeder, G J; White, M F ^[1]

---

1. Brigham and Women's Hospital, Boston, MA (USA) Harvard Medical School, Boston, MA (USA)

The authors have studied the function of a mutant insulin receptor (IR) molecule in which Try-1146, one of the first autophosphorylation sites in the {beta} subunit, was replaced with phenylalanine (IR{sub F1146}). Autophosphorylation of the partially purified IR{sub F1146} was reduced 60-70% when compared to the wild-type IR but was still stimulated by insulin. The phosphotransferase activity of the dephospho form of both the IR and IR{sub F1146} toward exogenous substrates was stimulated 3- to 4-fold by insulin. However, the wild-type IR was activated 12-fold by autophosphorylation, whereas the IR{sub F1146} was activated only 2-fold. When the IR{sub F1146} was expressed in Chinese hamster ovary (CHO) cells, ({sup 125}I)-insulin binding was normal, whereas autophosphorylation was reduced 80% when compared to cells expressing the wild-type IR. Endogeneous substrates of the insulin receptor kinase were not detected during insulin stimulation of CHO cells expressing the IR{sub F1146}. These data suggest that activation of the IR tyrosine kinase can be resolved into two components: the first is dependent on insulin binding and the second is dependent on the subsequent insulin-stimulated autophosphorylation cascade. Thus, at least two signal transduction pathways diverging from the IR are implicated in the mechanism of insulin action.

• OSTI ID: 5393994
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:9; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHO CELLS
DAYS LIVING RADIOISOTOPES
DNA
DNA BASE TRANSITIONS
DRUGS
ENZYME ACTIVITY
ENZYMES
EVEN-ODD NUCLEI
GROWTH
HORMONES
HYDROXY ACIDS
INSULIN
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MEMBRANE PROTEINS
METABOLISM
METHIONINE
MUTAGENESIS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
OLIGONUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDE HORMONES
PHENYLALANINE
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
RADIOISOTOPES
RECEPTORS
RECOMBINANT DNA
SULFUR 35
SULFUR ISOTOPES
TRANSFERASES
TYROSINE